In the pharmaceutical solid preparations, a sustained release film coating may sometimes be used for the purpose of reducing adverse drug reactions, reducing the dose frequency and enhancing drug effects. In another case, in the oral preparations containing a drug which degrades in a low pH environment, the preparations may be coated with an enteric film for the purpose of protecting the drug from the gastric acid. Accordingly, to sustained release the preparation containing a drug unstable in a low pH environment, it is essential to impart both functions of the protection from the gastric acid and the sustained release properties.
This type of film coating is commonly applied to tablets and granules, but it is mostly used for the spherical granules to control the performance uniformity. Meanwhile, the tablet is the most favored dosage form among patients in the pharmaceutical solid preparations. Thus, to obtain a tablet with controlled performance uniformity, it is desirable to formulate a tablet by adding other excipients to such a film coated granule.
The compression molding using a tableting machine is known as a typical manufacturing technique for formulating tablets. To secure practical production processes, handleability and transportability of the tablet, it is required to enhance the tablet hardness by the compression molding while applying a pressure to some extent. However, when tableting a film coated granule by the compression molding, the film layer (coating layer) is damaged by the pressure applied at the time of the compression molding, whereby the drug release-control performance and acid resistance required to the film layer are often deteriorated.
A variety of methods have been proposed to protect an enteric film layer from the mechanical stress applied during the tablet compression force. For example, a method has been proposed wherein a granule is coated with more than two film layers using two kinds of film coating agents having a film softening temperature difference of 50° C. or more, thereby reducing the film damages during the tablet compression force (e.g., see Patent Document 1). Further, another method has been proposed wherein the inner surface and the outer surface of an enteric film layer are coated with a cellulose-based coating agent to relieve the mechanical stress during the tablet compression force (e.g., see Patent Document 2).
Furthermore, an orally disintegrating tablet and the production method thereof have been proposed wherein a granule is coated with an enteric film coating agent containing a mixture of a methacrylic acid copolymer LD and an ethyl acrylate/methyl methacrylate copolymer dispersion and further coated with a coating layer containing a water soluble sugar alcohol such as mannitol, or the like (e.g., see Patent Document 3). By this technique, it is considered that the rough feeling and uncomfortable feeling is diminished when taking such a tablet and disintegration properties, solubility and acid resistance are considered to be improved.
On the other hand, a method for producing a sustained release tablet has been proposed wherein an elementary granule (a particle containing a drug) is coated by a single film layer using an enteric film coating agent and mixed with a pharmaceutical powder additive to formulate a tablet (e.g., see Patent Document 4).
Moreover, a production process which provides drug effects maintained for 24 hours is proposed (e.g., see Patent Document 5). In this production process, granules are first produced using a small content of a drug, an ethyl acrylate/methyl methacrylate copolymer dispersion, crystalline cellulose, and the like. Subsequently, the obtained granules are coated with a film coating agent independent of the pH of the mixture of a methacrylic acid copolymer LD and the ethyl acrylate/methyl methacrylate copolymer dispersion.
Furthermore, a film coating agent has been proposed wherein a methacrylic acid copolymer LD, an ethyl acrylate/methyl methacrylate copolymer dispersion, and a surfactant are polymerized (e.g., see Patent Document 6).
Patent Document 1Japanese Patent Application Laid-OpenNo. 8-109126Patent Document 2Japanese Patent Application Laid-OpenNo. 6-293635Patent Document 3Japanese Patent No. 3746167Patent Document 4Japanese Patent Application Laid-OpenNo. 4-169522Patent Document 5International publication No. WO2005/060939Patent Document 6National Publication of International PatentApplication No. 2005-522542